Publications by authors named "Amelia Ruffatti"

101 Publications

Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients.

Arthritis Res Ther 2021 05 4;23(1):134. Epub 2021 May 4.

AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'Ile de France, Paris, France.

Background: The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS.

Methods: We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks' gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit.

Results: The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus.

Conclusions: Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages.
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http://dx.doi.org/10.1186/s13075-021-02518-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094564PMC
May 2021

Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals.

Clin Rev Allergy Immunol 2021 Mar 16. Epub 2021 Mar 16.

Department of Medicine, Rheumatology Unit, University of Perugia, Piazzale Gambuli 1, 06132, Perugia, Italy.

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.
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http://dx.doi.org/10.1007/s12016-021-08857-2DOI Listing
March 2021

Markers of complement activation in plasma during quiescent phases in patients with catastrophic antiphospholipid syndrome.

Blood 2021 May;137(21):2989-2992

Rheumatology Unit, Department of Medicine, University Laboratories for Medical Research (LURM) University Hospital of Verona, Verona, Italy; and.

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http://dx.doi.org/10.1182/blood.2020010575DOI Listing
May 2021

The efficacy and safety of second-line treatments of refractory and/or high risk pregnant antiphospholipid syndrome patients. A systematic literature review analyzing 313 pregnancies.

Semin Arthritis Rheum 2021 02 17;51(1):28-35. Epub 2020 Dec 17.

Rheumatology Unit, Department of Medicine, University Hospital of Padua, Padua Italy; Internal Medicine Unit, Department of Medicine, San Bortolo Hospital, Vicenza, Italy.

Objective: The most efficacious strategy to manage pregnant patients with antiphospholipid syndrome (APS) refractory to conventional heparin/low-dose aspirin treatment or at high risk of adverse pregnancy outcomes has not been determined with any degree of certainty. The study set out to evaluate the efficacy and safety of the second-line treatments most frequently used in addition to conventional therapy, and the data were analyzed to identify which is/are associated to the best pregnancy outcomes.

Methods: A systematic review of the literature on studies concerning second-line treatments for refractory and/or high risk pregnant APS women published between February 2006 and February 2020 was conducted. The records were retrieved by searching Medline via Pubmed, the Web of Science platform, the Cochrane library database and clinicaltrials.gov.

Results: Fourteen studies met the eligibility criteria of the review: six retrospective cohort studies, one case-control, one case-series and six case reports. The results of single treatment protocols based upon hydroxychloroquine (HCQ), low-dose steroids (LDS), intravenous immunoglobulins (IVIG), plasma exchange (PE) or pravastatin and of combination protocols based upon HCQ+LDS, IVIG+LDS, PE+LDS and PE+IVIG used during 313 pregnancies in 303 APS women were analyzed and compared. The second-line treatments produced 261/313 (83.4%) live births; severe pregnancy complications were registered in 75/313 (24%) pregnancies. Drug side-effects were observed in 3/313 (0.9%) pregnancies. Statistical analysis identified a significantly higher live birth rate and/or a significantly lower number of severe complications in the pregnancies treated with IVIG, HCQ, pravastatin, PE+IVIG and PE+LDS.

Conclusion: Our results suggest using low-dose IVIG (< 2 g/Kg/month) or HCQ 400 mg/day starting before pregnancy in women with APS refractory to conventional therapy, while high-dose IVIG (2 g/Kg/month) associated with PE or alone in those with high risk±refractory APS.
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http://dx.doi.org/10.1016/j.semarthrit.2020.10.001DOI Listing
February 2021

The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts' Consensus.

Autoimmun Rev 2021 Feb 14;20(2):102738. Epub 2020 Dec 14.

Academic Rheumatology Unit, Dipartimento Di Medicina E Scienze, Della Salute "Vincenzo Tiberio", Università Degli Studi del Molise, Campobasso, Italy.

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients.
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http://dx.doi.org/10.1016/j.autrev.2020.102738DOI Listing
February 2021

The first thrombotic event in purely obstetric antiphospholipid syndrome patients and in antiphospholipid antibody carriers: comparison of incidence and characteristics.

Arch Gynecol Obstet 2021 02 3;303(2):455-461. Epub 2020 Sep 3.

Rheumatology Unit, Department of Medicine, University Hospital of Padua, Padua, Italy.

Purpose: The long-term risk of thrombosis after pregnancy in women with purely obstetric antiphospholipid syndrome (OAPS) is not well defined. The current study's primary outcome was to evaluate the incidence and characteristics of the first thrombotic event in OAPS, identifying the risk factors for thrombosis in OAPS was its secondary one.

Methods: Patients with purely OAPS were consecutively enrolled between September 1999 and September 2019. Subjects without a history of pregnancy morbidity or thrombosis but with persistent positivity for one or more antiphospholipid antibodies (aPL carriers) made up the control group. The study groups included 94 OAPS patients and 124 aPL carriers who were matched for clinical and laboratory parameters.

Results: An event rate of 0.49/100 patient years was registered in OAPS patients during a mean follow-up of 8.7 years ± 5.5 SD. Kaplan-Meier survival analysis revealed that the cumulative incidence of thromboembolic events was not significantly different in OAPS patients vs aPL carriers. Arterial thrombosis and cerebrovascular events were the more frequent types of vascular involvement in the two groups. As far as risk factors for thrombosis were concerned, the presence of lupus anticoagulant significantly prevailed in both thrombotic OAPS patients and thrombotic aPL carriers with respect to purely OAPS patients and aPL carriers who did not develop thrombosis (p = 0.01 and p = 0.00, respectively).

Conclusion: Just as for aPL carriers, closer monitoring and possibly, a pharmacological prophylaxis should be reserved for OAPS patients at highest risk of developing the first thrombotic event.
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http://dx.doi.org/10.1007/s00404-020-05766-1DOI Listing
February 2021

Fluorinated steroids are not superior to any treatment to ameliorate the outcome of autoimmune mediated congenital heart block: a systematic review of the literature and meta-analysis.

Clin Exp Rheumatol 2020 Jul-Aug;38(4):783-791. Epub 2020 Jun 23.

Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Italy.

Objectives: Fluorinated steroids are largely the therapeutic approach of autoimmune mediated congenital heart block (CHB). We performed a meta-analysis to assess the efficacy of fluorinated steroids for the treatment of CHB.

Methods: Studies evaluating the efficacy of fluorinated steroids versus no treatment in CHB patients were identified in electronic databases. Random-effects model was used to pool odds ratio (OR) (with 95% CI) of live births as the primary outcome. ORs of CHB progression, pacemaker implantation and extranodal disease were the secondary outcome. Subgroup analysis according to CHB grade and study type was performed.

Results: Data from nine studies involving 747 patients were analysed. The overall live birth rates were 86.8% and 86.7%, respectively, in the fluorinated steroids exposed foetuses and in the non-exposed ones. Fluorinated steroids did not ameliorate overall survival in CHB (OR 1.02; 95% CI: 0.65-1.61) with any significant statistical heterogeneity between studies (I2 0%, p=0.45). No significant differences for the progression of CHB, the pacing and the presence of extranodal disease were observed. Subgroup analysis revealed a significant protective role of fluorinated steroids for survival in 3rd degree CHB and for pacing in monocentric studies, OR 4.07; 95% CI: 1.10-15.08 and OR 0.15; 95% CI: 0.02-0.99, respectively.

Conclusions: This meta-analysis shows that fluorinated steroids are not superior to any treatment in patients with CHB in terms of live birth, prevention of progression of incomplete CHB, pacemaker implantation and extranodal disease. Thus, considering their side effects, their use in CHB patients should be discouraged.
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September 2020

Insights into the pathogenesis of catastrophic antiphospholipid syndrome. A case report of relapsing catastrophic antiphospholipid syndrome and review of the literature on ischemic colitis.

Clin Rheumatol 2020 Apr 18;39(4):1347-1355. Epub 2019 Dec 18.

Department of Cardiac, Thoracic Vascular Sciences and Public Health, University of Padua, Padua, Italy.

We present the case of a woman with a severe clinical history of antiphospholipid syndrome and persistent positivity for lupus anticoagulant, IgG anticardiolipin and IgG anti-β2Glycoprotein I antibodies. An acute clinical onset characterized by severe abdominal pain immediately followed by circulatory shock and histological colonic small vessel thrombosis pattern pointed to a diagnosis of ischemic colitis. The subsequent rapid onset of pulmonary alveolitis and heart failure associated to subendocardial hypoperfusion led to a diagnosis of definite catastrophic antiphospholipid syndrome (CAPS). Conventional triple therapy together with a broad-spectrum preventive antibiotic therapy were quickly initiated, and the outcome was favorable. We evaluated the patients with ischemic colitis in CAPS described in the literature between 1992 and May 2019 and our CAPS case. In accordance with the "two-hit" hypothesis and on the basis of the patients' data, we would like to speculate that the colonic wall necrosis related to ischemic colitis damaged the intestinal barrier causing loss of resistance to bacteria and leading to endotoxemia and bacteremia with bacteria translocation through the circulatory stream to the lungs and heart. The bacteria acted as the priming factor which favored the binding of β2Glycoprotein I to the endothelium vessels in the colon, lungs, and heart following activation of anti-β2Glycoprotein I antibodies which attached to the domain I of β2Glycoprotein I. This was followed by complement activation which triggered the thrombotic and cytokine storm. If further clinical studies confirm this hypothesis, the treatment of CAPS could be more targeted and effective.
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http://dx.doi.org/10.1007/s10067-019-04888-5DOI Listing
April 2020

Upgrading Therapy Strategy Improves Pregnancy Outcome in Antiphospholipid Syndrome: A Cohort Management Study.

Thromb Haemost 2020 Jan 21;120(1):36-43. Epub 2019 Oct 21.

Department of Medicine-DIMED, Rheumatology Unit, University of Padua, Padua, Italy.

The current study evaluates the efficacy and safety of different treatment strategies for pregnant patients with antiphospholipid syndrome. One hundred twenty-seven consecutive pregnancies were assessed; 87 (68.5%) with a history of pregnancy morbidity alone were treated with prophylactic low molecular weight heparin (LMWH) + low-dose aspirin (LDA, 100 mg) (group I) and 40 (31.5%) with a history of thrombosis and/or severe pregnancy complications with therapeutic LMWH + LDA (group II). LMWH doses were increased throughout the pregnancies depending on the patients' weight gain, and treatment was switched to a more intensive one at the first sign of maternal/fetal complications. The study's primary outcome was live births. There were no significant differences in live birth rate between group I (95.4%) and group II (87.5%). Even fetal complication rate was similar in the two groups; group II nevertheless had a higher prevalence of maternal and neonatal complications ( = 0.0005 and  = 0.01, respectively) and registered a significantly lower gestational age at delivery and birth weight ( = 0.0001 and  = 0.0005, respectively). Two patients in group I switched to group II therapy, six patients in group II switched to a more intensive treatment strategy (weekly plasma exchange + fortnightly intravenous immunoglobulins in addition to therapeutic LMWH + LDA). The multivariate analysis uncovered that triple antiphospholipid antibodies positivity was an independent factor leading to a more intensive therapy. All eight switched patients achieved a live birth. Study results revealed that adjusted LMWH doses and switching therapy at first signs of severe pregnancy complications led to a high rate of live births in antiphospholipid syndrome patients.
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http://dx.doi.org/10.1055/s-0039-1697665DOI Listing
January 2020

Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry.

Rheumatology (Oxford) 2020 06;59(6):1306-1314

Clinical Research Unit, Althaia Healthcare University Network of Manresa, University of Vic - Central University of Catalonia, Barcelona.

Objectives: To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS).

Methods: This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome.

Results: A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C).

Conclusion: Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.
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http://dx.doi.org/10.1093/rheumatology/kez419DOI Listing
June 2020

Therapeutic apheresis during pregnancy: A single center experience.

Transfus Apher Sci 2019 Oct 5;58(5):652-658. Epub 2019 Sep 5.

Rheumatology Unit, Department of Medicine - DIMED, University of Padua, Italy; Internal Medicine, San Bortolo Hospital, Vicenza, Italy.

Introduction: Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application.

Material And Methods: Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1).

Results: In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases.

Conclusions: Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.
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http://dx.doi.org/10.1016/j.transci.2019.07.009DOI Listing
October 2019

Complement activation in the plasma and placentas of women with different subsets of antiphospholipid syndrome.

Am J Reprod Immunol 2019 12 16;82(6):e13185. Epub 2019 Sep 16.

Department of Medicine, Rheumatology Unit, University Hospital of Padua, Padua, Italy.

Problem: As antiphospholipid antibody-positive women with adverse pregnancy outcomes have higher plasma complement activation product levels, and the placentas of women with antiphospholipid syndrome (APS) exhibit C4d complement component deposition, complement activation involvement has been hypothesized in APS pregnancy complications.

Method Of Study: Plasma levels of C5a and C5b-9 complement components of 43 APS non-pregnant patients and 17 pregnant APS women were measured using enzyme-linked immunosorbent assay. The results were compared with those of 16 healthy non-pregnant women and eight healthy pregnant women, respectively. Placenta samples of five APS patients at high risk of pregnancy complications and of five healthy controls were subjected to immunoblotting analysis with specific antibodies to C5b-9 and CD46, CD55, CD59 complement regulators.

Results: The mean plasma C5a and C5b-9 levels were significantly higher in the non-pregnant APS patients with previous thrombosis ± pregnancy morbidity (P = .0001 and P = .0034, respectively) and in the pregnant APS women with adverse outcomes (P = .0093 for both). Similarly, C5b-9 amounts were significantly higher in the adverse pregnancy outcome placenta (P = .0115) than in those associated to a favorable outcome. The mean CD46, CD55 and CD59 amounts were, instead, lower, although not always significantly, in the placentas of all the high-risk APS women with respect to the control placentas.

Conclusion: Data analysis demonstrated that there was significant complement activation in the more severe subset of APS patients and in only the adverse pregnancy outcome APS women. Further studies will clarify whether the lower CD46, CD55, and CD59 expressions in the APS placentas are limited to only high-risk APS patients.
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http://dx.doi.org/10.1111/aji.13185DOI Listing
December 2019

Triple Antiphospholipid (aPL) Antibodies Positivity Is Associated With Pregnancy Complications in aPL Carriers: A Multicenter Study on 62 Pregnancies.

Front Immunol 2019 14;10:1948. Epub 2019 Aug 14.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called "aPL carriers" (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers. Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded. An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84-247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose. This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.
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http://dx.doi.org/10.3389/fimmu.2019.01948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702797PMC
October 2020

An observational multicentre study on the efficacy and safety of assisted reproductive technologies in women with rheumatic diseases.

Rheumatol Adv Pract 2019 22;3(1):rkz005. Epub 2019 Feb 22.

Rheumathology and Clinical Immunology, ASST Spedali Civili and University of Brescia, Brescia.

Objectives: The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal-maternal complications) and whether, if performed, their efficacy is affected by maternal disease.

Methods: Sixty infertile rheumatic women undergoing 111 ART cycles were included. Clinical pregnancy rate, live birth rate, maternal disease flares and maternal-fetal complications were recorded.

Results: One hundred and eleven ART cycles in 60 women were analysed. We reported 46 pregnancies (41.4%), 3 (3.1%) cases of ovarian hyperstimulation syndrome and no cases of thrombosis during stimulation, pregnancy and puerperium. One or more maternal complication was reported in 13 (30.2%) pregnancies, and fetal complications occurred in 11 fetuses (21.1%). The live birth rate was 98%, but we reported three (6%) perinatal deaths in the first days of life. During puerperium, we recorded one (2.5%) post-partum haemorrhage and one (2.5%) articular flare.

Conclusion: The safety and efficacy of the ARTs, demonstrated in the general population, seems to be confirmed also in rheumatic patients. No evidence was found to advise against their application, and the choice of therapy should be made depending on the patient's risk profile, irrespective of whether the pregnancy is natural or artificial induced.
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http://dx.doi.org/10.1093/rap/rkz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649948PMC
February 2019

IgG phosphatidylserine/prothrombin antibodies as a risk factor of thrombosis in antiphospholipid antibody carriers.

Thromb Res 2019 May 8;177:157-160. Epub 2019 Mar 8.

Rheumatology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.

The clinical significance of IgG/IgM antiphosphatidylserine/prothrombin (aPS/PT) antibodies was prospectively evaluated in a cohort of 191 antiphospholipid antibody (aPL) carriers using commercial ELISA assays. IgG aPS/PT antibodies were detected in 40 (20.9%) and IgM aPS/PT in 102 (53.4%) of the carriers. Both IgG and IgM aPS/PT antibodies were significantly associated with triple aPL positivity (Lupus anticoagulants [LAC] plus anti-β2Glycoprotein I plus anticardiolipin antibodies) (p = 0.0000 for both). There was a significant prevalence of IgM aPS/PT in the individuals with isolated LAC positivity (p = 0.005). Fourteen of the aPL carriers (7.3%) developed a first thrombotic event. There was a significant prevalence of IgG aPS/PT antibodies but not of IgM aPS/PT in the thrombotic patients (p = 0.015). The cumulative incidence rate of thrombotic events was significantly higher in the IgG aPS/PT positive (p = 0.035) but not in the IgM aPS/PT positive carriers. Logistic regression analysis assessing the independent effect of IgG /IgM aPS/PT antibodies, triple aPL positivity, genetic/acquired thrombosis risk factors and autoimmune disorders on thrombosis development uncovered a significant association only for the risk factors (Odds Ratio = OR: 12.451, 95% Confidence Interval = CI: 2.519-61.537, p = 0.002) and for triple aPL positivity (OR: 4.725, 95% CI: 1.135-19.674, p = 0.033). Logistic regression evaluating the independent effect of IgG and IgM aPS/PT on thrombosis development uncovered a significant association only for the former (OR: 3.962, 95% CI: 1.174-13.37, p = 0.026). The risk score for thrombosis in aPL carriers could be more effective if IgG aPS/PT antibodies are added to triple aPL positivity and thrombosis risk factors.
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http://dx.doi.org/10.1016/j.thromres.2019.03.006DOI Listing
May 2019

First Report of the Italian Registry on Immune-Mediated Congenital Heart Block (Lu.Ne Registry).

Front Cardiovasc Med 2019 28;6:11. Epub 2019 Feb 28.

Unità di Reumatologia, Dipartimento di Medicina, Università di Padova, Padova, Italy.

Neonatal Lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro and anti-La/SSB autoantibodies to the fetus. The rarity of this condition requires the establishment of multidisciplinary registries in order to improve our knowledge. Inclusion criteria in this retrospective study were the maternal confirmed positivity for anti-SSA/Ro and/or anti-SSB/La antibodies, and the presence of II or III degree congenital heart block (CHB) or neonatal period (up to 27 days after birth). Eighty-nine cases of CHB were observed in 85 women with 88 pregnancies that occurred between 1969 and 2017. CHB was mostly detected (84 cases, 94.2%), while five cases were observed in the neonatal period. A permanent pacemaker was implanted in 51 of 73 children born alive (69.8), whereas global mortality rate was 25.8% (23 cases): 16 , five perinatal, and two during childhood. By univariate analysis, factors associated with fetal death were pleural effusion ( = 0.005, OR > 100; CI 95% 2.88->100 and hydrops ( = 0.003, = 14.09; CI 95% 2.01-122). Fluorinated steroids (FS) were administered in 71.4% pregnancies, and its use was not associated with better survival. Some centers treated all cases with fluorinated steroids and some centers did not treat any case. CHB was initially incomplete in 24 fetuses, and of them five cases of II degree block reverted to a lower degree block after treatments. Recurrence rate in subsequent pregnancies was 17.6% (3 out of 17). A prophylactic treatment was introduced in 10 of these 16 subsequent (58.8%) pregnancies, mostly with FS or high dose intravenous immunoglobulins. This is the first report from the Italian Registry of neonatal lupus/CHB. The live birth rate was nearly 80%, with nearly two thirds of the children requiring the implantation of a pacemaker. The management of fetuses diagnosed with CHB was heterogeneous across Italian Centers. The registry at present is mainly rheumatological, but involvement of pediatric cardiologists and gynecologists is planned.
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http://dx.doi.org/10.3389/fcvm.2019.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404544PMC
February 2019

Evidence of complement activation in the thrombotic small vessels of a patient with catastrophic antiphospholipid syndrome treated with eculizumab.

Autoimmun Rev 2019 05 4;18(5):561-563. Epub 2019 Mar 4.

Cardiac Surgery Unit, Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, Via Giustiniani, 2, 35, 128 Padua, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2019.03.015DOI Listing
May 2019

The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 1000 consecutive cases.

Autoimmun Rev 2019 Apr 15;18(4):406-414. Epub 2019 Feb 15.

Clinical Research Unit, Althaia Healthcare University Network of Manresa, Manresa, Barcelona, Spain.

Aim: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS).

Methods: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported.

Results: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in IIa, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%).

Conclusion: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.
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http://dx.doi.org/10.1016/j.autrev.2018.12.006DOI Listing
April 2019

Management of pregnant women with antiphospholipid antibodies.

Expert Rev Clin Immunol 2019 04 11;15(4):347-358. Epub 2019 Jan 11.

a Rheumatology Unit, Department of Medicine , University Hospital of Padua , Padua , Italy.

Introduction: Important advancements in pregnancy outcome have been reported in women with antiphospholipid antibodies (aPL), despite the fact that the treatment of aPL related pregnancy morbidity is not guided by consistent findings from well-designed trials. Areas covered: The current study draws a picture of the studies in the literature by performing a Medline search of relevant English language articles and reports our experience in managing different subsets of obstetric antiphospholipid syndrome (APS), defined on the basis of their clinical and laboratory characteristics. The management of pregnant women with non-criteria APS manifestations and that of aPL carriers during their first pregnancy is also examined. Expert commentary: A heparin/aspirin combination constitutes conventional treatment for APS affected pregnant women. As this strategy fails in approximately 20-30% of cases, uncovering other options for women refractory to conventional treatment or at high risk of pregnancy complications has become an urgent undertaking. Some attempts have been made to prescribe additional treatments in the effort to improve live birth rates and/or reduce pregnancy complications, which often occur even in patients treated conventionally. The evidence from some studies and an individual risk/benefit assessment should instead guide treatment decisions for pregnant patients with non-criteria APS manifestations and aPL carriers.
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http://dx.doi.org/10.1080/1744666X.2019.1565995DOI Listing
April 2019

"Disease knowledge index" and perspectives on reproductive issues: A nationwide study on 398 women with autoimmune rheumatic diseases.

Joint Bone Spine 2019 07 21;86(4):475-481. Epub 2018 Dec 21.

Rheumatology Unit, Department of Medicine, University of Perugia, Piazzale Gambuli, 1, 06132 Perugia, Italy.

Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age.

Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149).

Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning.

Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.
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http://dx.doi.org/10.1016/j.jbspin.2018.12.002DOI Listing
July 2019

HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome.

Autoimmun Rev 2018 Dec 12;17(12):1153-1168. Epub 2018 Oct 12.

MITOVASC institute and CARFI facility, UMR CNRS 6015, INSERM U1083, University of Angers, Angers, France.

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
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http://dx.doi.org/10.1016/j.autrev.2018.05.012DOI Listing
December 2018

Catastrophic antiphospholipid syndrome: Lessons from 14 cases successfully treated in a single center. A narrative report.

J Autoimmun 2018 09 7;93:124-130. Epub 2018 Jul 7.

Cardiology Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.

The study aimed to evaluate the clinical significance of laboratory findings in patients with catastrophic antiphospholipid syndrome (CAPS) and to report the effects of a well-defined treatment protocol in 14 consecutive cases. Thirteen patients (12 presenting one and one presenting two episodes of CAPS) were consecutively treated and monitored between 1986 and 2017. Antiphospholipid antibody (aPL) characteristics of the patients were compared with those of 64 matched controls (45 antiphospholipid syndrome patients and 19 aPL carriers) who did not develop CAPS during the same mean follow-up period (12 years ± 9.9 SD). Triple aPL positivity (IgG/IgM anticardiolipin + IgG/IgM anti-β2Glycoprotein I + lupus anticoagulants) significantly prevailed in the CAPS patients with respect to the controls (p = 0.003). IgG anticardiolipin and IgG anti-β2Glycoprotein I mean antibody titers of the CAPS patients were significantly higher than those of the controls (p = 0.0018 and p = 0.003, respectively). Triple therapy (anticoagulation + plasma exchange + steroids) was administered to all the CAPS cases except for one. Beginning in 2009, intravenous immunoglobulin infusion has also been included in the triple therapy protocol (six patients). All the patients recovered from CAPS; five showed renal failure and one a I-II class New York Heart Association (NYHA) dilated cardiomyopathy. Long-term outcomes of CAPS included a gradual worsening of renal failure in one patient who required hemodialysis 30 years after the acute episode. Renal function improved in the other four patients. The patient affected with dilated cardiomyopathy worsened to a II class NYHA over a five year period. Currently all the patients are alive. A specific antiphospholipid antibody profile could be considered a risk factor associated to CAPS. Early use of a defined treatment protocol based on triple therapy either or not associated with IVIG was associated with recovery in all CAPS patients.
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http://dx.doi.org/10.1016/j.jaut.2018.07.001DOI Listing
September 2018

Antiphosphatidylserine/prothrombin Antibodies in Antiphospholipid Syndrome with Intrauterine Growth Restriction and Preeclampsia.

J Rheumatol 2018 08 15;45(9):1263-1272. Epub 2018 Jul 15.

From the Istituto Scientifico Ospedale San Raffaele; Vita-Salute San Raffaele University, Milan; Department of Clinical and Experimental Medicine, Rheumatology Unit, University of Padua, Padua, Italy.

Objective: Antibodies that recognize the phosphatidylserine/prothrombin complex (antiphosphatidylserine/prothrombin antibodies; aPS/PT) might reveal enhanced thrombotic risk in patients with systemic lupus erythematosus. Little is known about their association with pregnancy complications in the antiphospholipid syndrome (APS).

Methods: We enrolled 55 patients with APS who were seeking pregnancy in 2 Italian hospitals. Antiphospholipid antibodies (aPL), including anticardiolipin antibodies, anti-β-glycoprotein I antibodies, lupus-like anticoagulant, and aPS/PT antibodies were assessed, and the patients were prospectively followed for 24 months.

Results: There were 65% (36/55) of the APS patients who had aPS/PT antibodies. Forty-seven pregnancies were followed, including 33 of aPS/PT+ patients. Forty-one of the 47 patients (87%) who initiated a pregnancy eventually gave birth to a child. The pregnancy duration and the mean newborn weight at delivery were significantly lower in aPS/PT+ than in aPS/PT- patients (33.1 ± 4.7 vs 36.2 ± 3.4 wks of gestation, respectively, and 2058 ± 964 g vs 2784 ± 746 g, respectively, p < 0.05). Late pregnancy complications, including intrauterine fetal death, preterm delivery, preeclampsia, and intrauterine growth restriction (IUGR), were more frequent in aPS/PT+ patients, independent of the therapy. Titers of aPS/PT IgG were significantly inversely correlated with the neonatal weight at delivery. Vascular injury, as reflected by thrombosis, fibrinoid necrosis, ischemic and hemorrhagic areas, and presence of chorangiomas characterized the IUGR placentas in the presence of aPS/PT.

Conclusion: The aPS/PT antibodies might represent markers of aPL-related pregnancy complications, IUGR/preeclampsia in particular, and could help identify beforehand patients who may require additional treatment.
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http://dx.doi.org/10.3899/jrheum.170751DOI Listing
August 2018

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome.

Blood 2018 09 12;132(13):1365-1371. Epub 2018 Jul 12.

Cardiology Clinic, Thrombosis Centre, Department of Cardiac Thoracic and Vascular Sciences, and.

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.
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http://dx.doi.org/10.1182/blood-2018-04-848333DOI Listing
September 2018

Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study.

Thromb Haemost 2018 04 28;118(4):639-646. Epub 2018 Feb 28.

Louise Coote Lupus Unit, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, United Kingdom.

The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The study's inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-β2 glycoprotein I antibodies; (2) a history of severe maternal-foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal-foetal complications (Group II). Two different additional treatments were considered: oral-low-dose steroids (10-20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral-intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The study's primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine ( = 0.036) and its administration before versus during pregnancy ( = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones ( = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.
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http://dx.doi.org/10.1055/s-0038-1632388DOI Listing
April 2018

Beyond thrombosis: Anti-β2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome.

J Autoimmun 2018 06 14;90:76-83. Epub 2018 Feb 14.

Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy; Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095 Cusano Milanino, Milan, Italy; Department of Rheumatology, ASST Istituto Gaetano Pini & CTO, Piazza Cardinal Ferrari, 1 20122 Milan, Italy. Electronic address:

Antibodies against β2 glycoprotein I (anti-β2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and conformation-dependent structure on β2GPI domain (D) 1. Anti-β2GPI domain profiling has been investigated in thrombotic APS, leading to the identification of antibodies targeting D1 as the main subpopulation. In contrast, scarce attention has been paid to obstetric APS, hence this study aimed at characterizing the domain reactivity with regards to pregnancy morbidity (PM). To this end, 135 women with persistently positive, medium/high titre anti-β2GPI IgG, without any associated systemic autoimmune diseases and at least one previous pregnancy were included: 27 asymptomatic carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash β2GPI Domain 1 IgG and QUANTA Lite β2GPI D4/5 IgG, Inova Diagnostics). Positivity for anti-D1 antibodies, but not anti-D4/5 antibodies, was differently distributed across the 4 subgroups of patients (p < 0.0001) and significantly correlated with thrombosis (χ2 = 17.28, p < 0.0001) and PM (χ2 = 4.28, p = 0.039). Patients with triple positivity for anti-phospholipid antibodies displayed higher anti-D1 titres and lower anti-D4/5 titres compared to women with one or two positive tests (p < 0.0001 and p = 0.005, respectively). Reactivity against D1 was identified as a predictor for PM (OR 2.4, 95% confidence interval [CI] 1.2-5.0, p = 0.017); in particular, anti-D1 antibodies were predictive of late PM, conveying an odds ratio of 7.3 (95% CI 2.1-25.5, p = 0.022). Positivity for anti-D1 antibodies was not associated with early pregnancy loss. Anti-D4/5 antibodies were not associated with clinical APS manifestations. As a whole, our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis, but also with late PM, while positive anti-D4/5 antibodies are not predictive of thrombosis or PM.
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http://dx.doi.org/10.1016/j.jaut.2018.02.002DOI Listing
June 2018

The treatment of anti-phospholipid syndrome: A comprehensive clinical approach.

J Autoimmun 2018 06 13;90:1-27. Epub 2018 Feb 13.

Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095 Cusano Milanino, Milan, Italy.

Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease that predisposes to thrombotic events and/or obstetric complications, in the persistent presence of anti-phospholipid antibodies (aPL). Life long moderate-intensity anticoagulation is the option of choice for aPL-positive patients with a previous thrombosis; critical issues concern the management of those with a history of arterial event due to the high rate of recurrence. Alternatives comprise anti-platelet agents and high-intensity anticoagulation. Low dose aspirin (LDASA) and low molecular weight heparin provide the mainstay of the treatment of obstetric APS, allowing a birth rate in 70% of cases. The management of refractory APS, thrombotic as well as obstetric, is highly debated, but an increasing burden of evidence points towards the beneficial effects of multiple treatments. Similarly, a management envisaging multiple drugs (anticoagulation, steroids, plasma exchange and/or intravenous immunoglobulins) is the most effective approach in catastrophic APS. Asymptomatic aPL carriers are at higher risk of thrombotic and obstetric complications compared to the general population, thus potentially benefitting of a pharmacological intervention. LDASA and hydroxychloroquine can be considered as options, in particular in case of high risk aPL profile, concomitant cardiovascular risk factors or associated autoimmune disease. APS is apparently a simple condition, but its multifaceted nature requires a complex and tailored treatment.
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http://dx.doi.org/10.1016/j.jaut.2018.02.003DOI Listing
June 2018

Detection of autoantibodies to the p200-epitope of SSA/Ro52 antigen. A comparison of two laboratory assays.

Clin Chem Lab Med 2018 05;56(6):927-932

Rheumatology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.

Background: Anti-p200 antibodies have been receiving growing interest in view of findings associating their presence to risk of fetal autoimmune congenital heart block (CHB). The study compares and evaluates the performance of two assays currently being used for their detection.

Methods: One hundred and sixteen pregnant women positive for anti-SSA/Ro52 antibodies were considered as the study population. Fifty women negative for anti-SSA/Ro52 antibodies were considered as the control population. Anti-p200 antibodies were analyzed using two home-made ELISA assays: one with biotinylated antigen and the other with free antigen.

Results: The specificity of the p200-free assay was significantly higher with respect to that of the p200-biotin assay (p=0.023). Both methods showed a high area under curve (AUC), thus, a good accuracy. There was a significant prevalence of anti-p200 antibodies when the p200-free assay was used to analyze the sera of the pregnant women with CHB fetuses (p=0.007). Cohen's κ and Spearman's ρ coefficients showed a good concordance (0.71) and a high correlation (0.93), respectively.

Conclusions: The p200-free assay with respect to the biotin-based method was more specific in detecting p200 antibodies in women positive for anti-SSA/Ro52 antibodies. In addition, only the p200-free method significantly found p200 antibodies in patients with fetal CHB.
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http://dx.doi.org/10.1515/cclm-2017-0704DOI Listing
May 2018

Comparative study between obstetric antiphospholipid syndrome and obstetric morbidity related with antiphospholipid antibodies.

Med Clin (Barc) 2018 09 20;151(6):215-222. Epub 2017 Dec 20.

AP-HP, Hôpital Saint-Antoine, service de médecine interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, F-75012, Paris, France.

Background And Objectives: To compare clinical, laboratory, treatment and live birth rate data between women with aPL-related obstetric complications (OMAPS) not fulfilling the Sydney criteria and women fulfilling them (OAPS).

Materials And Methods: Retrospective and prospective multicentre study. Data comparison between groups from The European Registry on Antiphospholipid Syndrome included within the framework of the European Forum on Antiphospholipid Antibody projects.

Results: 338 women were analysed: 247 fulfilled the Sydney criteria (OAPS group) and 91 did not (OMAPS group). In the OMAPS group, 24/91 (26.37%) fulfilled laboratory Sydney criteria (subgroup A) and 67/91 (74.63%) had a low titre and/or non-persistent aPL-positivity (subgroup B). Overall, aPL laboratory categories in OAPS vs. OMAPS showed significant differences: 34% vs. 11% (p<0.0001) for category I, 66% vs. 89% (p<0.0001) for category II. No differences were observed when current obstetric complications were compared (p=0.481). 86.20% of OAPS women were treated vs. 75.82% of OMAPS (p=0.0224), particularly regarding the LDA+LMWH schedule (p=0.006). No differences between groups were observed in live births, gestational, puerperal arterial and/or venous thrombosis.

Conclusions: Significant differences were found among aPL categories between groups. Treatment rates were higher in OAPS. Both OAPS and OMAPS groups had similarly good foetal-maternal outcomes when treated. The proposal to modify OAPS classification criteria, mostly laboratory requirements, is reinforced by these results.
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http://dx.doi.org/10.1016/j.medcli.2017.11.017DOI Listing
September 2018
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